United Abominations is released

In May 2006 Megadeth announced their eleventh studio album, entitled United Abominations, was near completion.

Originally scheduled for release by Roadrunner Records in October 2006, Mustaine announced in August 2006 that the band were "putting the finishing touches on it", and it was rescheduled for release on May 15, 2007. United Abominations is the band's first studio release to feature members Glen Drover, Shawn Drover, and James Lomenzo. In March 2007 Dave Mustaine announced at the Megadeth forums that a new version of "À Tout le Monde (Set Me Free)" would be released on the album. It features a duet with Cristina Scabbia of the band Lacuna Coil, and was to be the first single from the album until it was replaced by "Washington Is Next!".

United Abominations was released on May 15, 2007. It debuted a week later at #8 in the US, the band's highest charting position since 1994's Youthanasia, and sold 54,000 copies in its first week. In March 2007 Megadeth commenced a tour through Canada and the United States as an opening act for the newly-reformed Heaven and Hell, along with Down on Canadian dates and Machine Head on US dates, followed by a summer festival tour through Europe. In September 2007 Megadeth returned to the United States as the headline act on their Tour Of Duty tour, which also included the Pacific rim and the third installment of Gigantour which was launched in Australia in November 2007, line up included Static-X, Lacuna Coil, DevilDriver and Bring Me the Horizon.

On January 13, 2008, Dave Mustaine confirmed that Glen Drover had quit Megadeth to focus on his family, and was replaced by Chris Broderick (formerly of Nevermore and Jag Panzer). The new line-up made its live debut in Finland on February 4, went on Tour Of Duty tour in Europe as the headline act and returned to UK the same month and US in the spring for Gigantour 2008. Dave Mustaine wanted a shorter lineup so each band had a good chance to put on a show. The 2008 installment of the tour featured In Flames, Children of Bodom, Job for a Cowboy, and High on Fire (and Evile for the UK and Scandinavia tour). Also Megadeth did Tour Of Duty tour in South America and Mexico in May and June 2008. Commenting on leaving the band, Drover said "I am aware of the rumors that I left Megadeth to focus on family life. My family life has always been my priority. In the end, I was unhappy with the situation, which magnified me wanting to spend more time with my family and realizing that it's time for me to move on to the next chapter in my musical career, I have a lot of great memories and met a ton of great people along the way, both fans and people in the industry."

Mustaine said he is happy with Drover's decision and is pleased that his replacement is Broderick. Mustaine also said "Chris is doing just fine." Former Nevermore bandmate Van Williams commented that Megadeth is "getting one hell of a good player, more importantly they're getting a great guy to hang out with and a true friend." Broderick said "I realize I have some big shoes to fill and I will do my best." With regards to what kind of an addition Chris Broderick will be for Megadeth, Dave Mustaine in an interview said "...thoroughly thrilled with Chris... it reminds me a lot like when Ozzy found Randy Rhoads." A compilation album called Anthology: Set The World Afire was released on September 30, 2008.